Mouse model of chronic and binge ethanol feeding (the NIAAA model)

• Published in: Nature protocols Vol. 8; no. 3; pp. 627 - 637
• Main Authors: Bertola, Adeline, Mathews, Stephanie, Ki, Sung Hwan, Wang, Hua, Gao, Bin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2013; Nature Publishing Group
• Subjects: 631/1647/334/1874/345; 631/1647/767/1424; 64/60; 692/699/1503/1607/1608; Alcoholism; Alcoholism - pathology; Alcohols; Analytical Chemistry; Animals; Binge Drinking - pathology; Biological Techniques; Blood; Causes of; Computational Biology/Bioinformatics; Diet; Disease Models, Animal; Drinking of alcoholic beverages; Drinking water; Ethanol; Ethanol - pharmacology; Feeding; Health aspects; Hepatitis; Hepatoma; Inflammation; Laboratories; Life Sciences; Liver; Liver cirrhosis; Liver diseases; Liver Diseases, Alcoholic - pathology; Male; Mice; Mice, Inbred C57BL; Microarrays; Mortality; National Institute on Alcohol Abuse and Alcoholism (U.S.); Organic Chemistry; Pathogenesis; protocol; United States; United States
• ISSN: 1754-2189; 1750-2799; 1750-2799
• DOI: 10.1038/nprot.2013.032

Chronic alcohol consumption is a leading cause of chronic liver disease worldwide, leading to cirrhosis and hepatocellular carcinoma. Currently, the most widely used model for alcoholic liver injury is ad libitum feeding with the Lieber-DeCarli liquid diet containing ethanol for 4–6 weeks; however, this model, without the addition of a secondary insult, only induces mild steatosis, slight elevation of serum alanine transaminase (ALT) and little or no inflammation. Here we describe a simple mouse model of alcoholic liver injury by chronic ethanol feeding (10-d ad libitum oral feeding with the Lieber-DeCarli ethanol liquid diet) plus a single binge ethanol feeding. This protocol for chronic-plus-single-binge ethanol feeding synergistically induces liver injury, inflammation and fatty liver, which mimics acute-on-chronic alcoholic liver injury in patients. This feeding protocol can also be extended to chronic feeding for longer periods of time up to 8 weeks plus single or multiple binges. Chronic-binge ethanol feeding leads to high blood alcohol levels; thus, this simple model will be very useful for the study of alcoholic liver disease (ALD) and of other organs damaged by alcohol consumption.